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Is α7-nAChR a possible target for lung cancer and malignant pleural mesothelioma treatment?
Alfredo Cesario1, Patrizia Russo, Candida Nastrucci
1Laboratory of Systems Approaches and Non Communicable Diseases, IRCCS San Raffaele Pisana, Via di Val Cannuta 247-249, 00166 Rome, Italy.
Abstract:
This paper discusses the potential therapeutic effect of α7-nAChR antagonists for NSCLC (non small cell lung cancer) and MPM (malignant pleural mesothelioma). This therapeutic approach is based on the experimental observations that: (a) functional α7-nAChR are expressed in NSCLC and MPM cells, (b) the activation of these receptors by agonists, namely nicotine, induces cell proliferation and inhibits apoptosis, whereas antagonists have a pro-apoptotic effect. Among competitive α7-nAChR antagonists, d-tubocurarine and -cobratoxin (α-CbT), from the snake venom of Naja, emerged as possible drug candidates. However, some aspects of the samples must be particularly taken into account, such as the particular nature of the sample. Thus, when using natural compounds purified from snake venom, it is important to take into account the factors such as whether the venom sample was derived from different animals, purified by different methods, or contained contaminants of the same molecular weight. Finally, biological activity may be different for different batches, which could also have been stored under different conditions (e.g. temperature, dilution, suspension medium etc.). These factors, affecting the experimental results, are also discussed.
Insights
Alpha-7 nicotinic acetylcholine receptor (α7-nAChR) antagonists show therapeutic potential for non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). These compounds may induce apoptosis in cancer cells, offering a novel treatment strategy.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Functional alpha-7 nicotinic acetylcholine receptors (α7-nAChRs) are expressed in non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM) cells.
- Receptor activation by agonists like nicotine promotes cancer cell proliferation and inhibits apoptosis.
- Conversely, α7-nAChR antagonists demonstrate a pro-apoptotic effect on these cancer cells.
Purpose of the Study:
- To explore the therapeutic potential of α7-nAChR antagonists for treating NSCLC and MPM.
- To identify potential drug candidates, specifically d-tubocurarine and α-cobratoxin (α-CbT) from Naja snake venom.
Main Methods:
- Review of experimental observations regarding α7-nAChR expression and function in NSCLC and MPM.
- Evaluation of d-tubocurarine and α-cobratoxin as competitive α7-nAChR antagonists.
- Discussion of critical factors influencing the experimental results of natural compounds.
Main Results:
- α7-nAChR antagonists exhibit a pro-apoptotic effect on NSCLC and MPM cells.
- D-tubocurarine and α-cobratoxin are identified as potential therapeutic agents.
- Variability in venom sample origin, purification methods, contaminants, batch consistency, and storage conditions can impact biological activity.
Conclusions:
- α7-nAChR antagonists represent a promising therapeutic avenue for NSCLC and MPM.
- Careful consideration of natural compound sample characteristics is crucial for reproducible and reliable experimental outcomes.
- Further research into optimizing the use of snake venom-derived compounds is warranted.
